Gangliosides are cell surface glycosphingolipids expressed abundantly by most malignant melanomas and other cancers of neuroectodermal origin. Three gangliosides, the disialogangliosides GD3 and GD2 and the monosialoganglioside GM2, have proven to be of particular interest to tumor immunologists for a variety of reasons. GD3 is recognized by several mouse monoclonal antibodies but by no sera or monoclonal antibodies of human origin. GD2 and GM2 are reactive with sera from some melanoma patients and some normal donors and have recently been detected by mouse and human monoclonal antibodies. From the pattern of cellular distribution in normal and malignant tissues, it appears that GD3, GD2, and GM2 have the characteristics of differentiation antigens of neuroectodermal origin. Interest in these antigens was intensified by the observation that there was regression of melanoma and neuroblastoma metastases in some patients treated with anti-GD3 and anti-GD2 mouse monoclonal antibodies indicating that cell surface gangliosides may be targets for cancer therapy.
Gangliosides play critical roles in cell-cell interactions as differentiation markers and receptors for toxins, hormones and other factors. Malignant transformation frequently results in changes in ganglioside pattern and the importance of ganglioside for detection and treatment of cancer has recently been established. However, gangliosides are rarely immunogenic, thwarting attempts at active immunization or production of monoclonal antibodies. Association of poorly immunogenic or tolerated antigens with immunostimulating complexes is a method of augmenting immunogenicity. GM2 is used as a model for all gangliosides. The relative immunogenicity of the different ganglioside preparations may be determined in mice and methods to further increase their immunogenicity in various types of vaccines determined. Approaches shown to be optimal for GM2 are applicable to GD2, GD3, GM3 analogues and derivatives thereof (including O-acetyl GD3) and other gangliosides.
It has now been discovered that a "small" liposome, that is a liposome with a diameter of about 500 nm or less, with incubation associated immuno-potentiators such as Lipid A is an improved adjuvant, as measured by the anti-GM2 titer of animal sera obtained after inocculation with such liposomes containing incubation associated Lipid A and GM2.